This SSC intervention project in mothers and their full-term infants is a RCT with two parallel groups (intervention versus passive control group). The study has been designed in accordance with the SPIRIT 2013 statement (see Additional file 1 for complete checklist) . Administrative information related to the trial can be obtained in Additional file 2. The project will start in April 2016. The expected total duration of the study from the start of recruitment to the last participant finishing the 1-year assessment is 20 months. The study will start with baseline measures in the last trimester of pregnancy. The intervention period will start immediately after birth and will have a duration of 5 weeks. Maternal and infant outcomes will be measured at 2 weeks, 5 weeks, 12 weeks and 1 year after birth.
The trial has been approved by the ethics committee of the Social Science faculty of the Radboud University in Nijmegen, The Netherlands (ECSW2015–2311-358). Modifications to the protocol, including changes of study objectives, study design, population, sample sizes, study procedures, or significant administrative aspects will require a formal amendment to the protocol. The potential amendment will be examined and approved by the ethics committee of the Social Science faculty of the Radboud University prior to implementation. Modifications to the protocol will also be included in the formal trial registration at the Dutch Trial Registration (NTR). This study does not involve any harmful procedures or adverse events. Since trial-related harm is negligible no provisions will be included, the study will not be audited, and no data-monitoring committee will be needed. Although we do not expect that the participants will experience trial-related harms, mothers will be asked weekly, for the first 5 weeks after birth, about any problems and mothers will be encouraged to report harms or adverse events spontaneously. Also, during the home visit in week 5 we will ask mothers to report any previously unreported harmful or adverse events that occurred during the study trial. Answers will be assessed by the investigators and will be reported in study reports. In addition, all participants that are enrolled in the study will be covered by the indemnity for negligent harm insurance (standard arrangements of the Behavioural Science Institute, Radboud University, Nijmegen, The Netherlands).
Sample size calculation
The sample size was calculated with a power analysis, using the G Power 3 online tool . The effect size of f = .24 for maternal depressive symptoms was based on the study of Bigelow and colleagues and was calculated by using the mean levels and the pooled standard deviation of maternal depressive symptoms for the SSC and the control group . The power analysis indicated that a total group size of 84 mother-infant dyads was required to maintain a power of 80% to detect a minimum effect size of f = .24 for maternal depressive symptoms with a significance level of 0.05. Based on a prior longitudinal study in a similar population , we assume that 14% of the mothers will sign up to the study but will never participate. Based on the same longitudinal study , we calculated that the drop-out rate will be 4% and the loss in follow up rate will be 9%. Additionally, we estimate a non-compliance rate of 10%. In total, we need to include 31 additional pregnant women in order to retain power. To maintain equal groups we will recruit 116 participants (58 mothers and their infants in each arm).
A total sample of 116 healthy expectant mothers will be recruited during pregnancy in the region of the Radboud University, The Netherlands. In this region, 17.800 children are born every year . Pregnant women have to meet the following eligibility criteria: age ≥ 18, singleton pregnancy, no drug use during pregnancy, no severe physical or mental health problems, and sufficient understanding of the Dutch language. Also, exclusive participation in this intervention trial is required. The infants have to be born at ≥37 weeks of pregnancy and have to meet the following eligibility criteria: no congenital anomalies, birth weight ≥ 2500 g, and 5-min Apgar score ≥ 7. The participant flow is displayed in Fig. 1.
Tables 1 and 2 show the maternal and infant primary and secondary outcomes at the different time points. Table 3 shows the additional information, such as the demographics and confounders that will be collected in the current study.
See Table 4 and Fig. 2 for details of the study procedure.
The recruitment includes a cover story. Mothers will be told that the study will focus on the relationships between infant sleep and feeding behavior, mother-infant contact, and maternal and infant mental and physical health. In addition, the mothers will be told that a subgroup of the pregnant women will be asked to implement a natural and simple 5-week daily contact period with their newborn infant, starting immediately after birth.
Women will be recruited from a database of pregnant women who have expressed their interest for participating in scientific research. In addition, the experimenter will recruit women at pregnancy clubs, baby fairs, and baby shops. All expectant women will be informed about the study with the study flyer and study website.
After signing up, all expectant mothers will be telephoned by the principle investigator to provide more information about the study. The eligibility questionnaire will assess the eligibility of the mother. Next, a home visit in late pregnancy (week 34–36) will be arranged for interested and eligible women to explain the study in person by the principle investigator.
Primiparous mothers are expected to have more opportunities to provide SSC to their infants compared to multiparous mothers. A stratified random block randomization method will ensure a balance between the SSC and the control condition for the primiparae versus multiparae mothers. Also, this randomization method produces comparable groups by avoiding confounding from known and unknown factors . The block sizes will be randomly chosen from the set of 4 and 6. Randomization will be with a 1:1 allocation. An independent researcher, who is not involved in the study, will prepare this schedule by a computerized randomisation program and will conceal the allocation sequence in stapled envelopes. The allocation sequence will be concealed from the researcher enrolling and assessing participants. The mothers will be included in the study after signing the informed consent, regarding the use of participant data and biological samples (see Additional file 3 for the Dutch versions of the informed consent form and information statement for participants), and filling out the medical checklist during the pregnancy home visit. Hereafter, the principal investigator will open the envelope and the mothers in the SSC group will be informed about their group allocation. Participants and the principle investigator will not be blinded for the group allocation.
Intervention and control condition
The study of Bigelow and colleagues requested their mothers to provide at least 6 h of SSC per day in the first week after birth and continue with at least 2 h of SSC per day until the infant was one moth of age . However, many mothers did not meet the SSC criterion. In this study we reduce the amount of requested hours and extend the number of requested weeks of daily SSC to enlarge the number of mothers that meet the SSC criterion. In the Netherlands mothers are entitled to at least 10 weeks of paid maternity leave after delivery, which will facilitate adherence to our adapted SSC protocol. During the instruction phase of the pregnancy home visit, all mothers in the intervention group will be provided with detailed written and oral instructions on SSC. We will request and encourage mothers in the SSC condition to provide their infants with at least one uninterrupted hour of maternal SSC, on a daily basis and for 5 weeks, starting immediately after birth. Other caregivers are allowed to provide supplementary hours of SSC to the infant. The period of one uninterrupted hour is based on two arguments. First, the average duration of the sleep cycle of healthy full-term infants is 47 min . The requested uninterrupted hour decreases the chance that infants need to be disturbed in the middle of a sleep cycle. Second, shorter SSC episodes could potentially decrease or eliminate the effectiveness of SSC, since undressing and dressing can be defined as a mild physical stressor for infants . The requested uninterrupted hour requires to undress and dress the infant only once. During SSC, the naked infant, wearing only a diaper, will be placed in a stable and upright position between the breasts of the mother to facilitate and maximize SSC. The head of the infant is positioned in a slightly upright position to keep the airway open. After, the infant and mother will be covered by a blanket or cardigan (see also the practical guidelines of the World Health Organization ). Mothers in the SSC condition will explicitly be asked to feed their child before SSC. However, we will not discourage breastfeeding during SSC. During the oral and written instructions, we will explain safety precautions during SSC. We will emphasize the importance of being awake and alert during SSC, and of avoiding drinking hot beverages during SSC to protect the infant. During the second home visit (week 5 after birth), we will ask mothers whether they experienced problems with the safety precautions. Mothers in the control condition will not be requested and encouraged to provide SSC to their infant.
Mother in both groups will fill out the same daily contact logbook. In the daily logbook, all mothers will be asked to register for every 15 min with simple lines the following three categories: 1) holding, 2) SSC, and 3) no contact. In this logbook, mothers are also able to discriminate between holding and SSC by the mother or other caregivers, for example the father or grandparents.
Upon signing the informed consent, participants are informed that they may decide to discontinue the study at any moment and without giving a reason. Several measures are taken in order to minimize attrition and maintain adherence to the study. During the 5-week trial period, the principal investigator will have weekly contact with the participating mothers. Participants will be reminded of the upcoming data collection and they will be asked about any problems they are having with skin-to-skin contact, in filling out the logbooks, or with the collection of the stool samples. In addition, to improve participant retention the mothers will receive a small present after birth, and a present and a financial reimbursement of 20 euros at the home visit in week 5. Last, the mothers will receive the study-wide results after publication of the study reports.
Pregnancy home visit
One day before the pregnancy home visit, an e-mail will confirm the home visit. During this visit, the researcher reconfirms eligibility. Based on the cover story, the experimenter will provide additional information about the study. If mothers are still interested, informed consent is obtained by the principle investigator and mothers will fill out the medical checklist. Next, the SSC group will be informed about the group allocation. Expectant mothers in the SSC group will receive detailed instructions on SSC. All expectant mothers will receive the information statement with a summary of the instructions about the prenatal and postnatal part of the study. Also, the experimenter will explain how the study logbooks and questionnaires need to be filled out, and how the samples need to be collected. Additionally, the mother will be asked about her preference related to the communication during the intervention period (e-mail versus text-message). Lastly, the mother will fill out the prenatal questionnaires.
Five-week intervention period starting at birth
The mother will be asked to inform the researcher of the baby’s birth by e-mail, text message or telephone. Five days after birth, the researcher will telephone all mothers to assess the eligibility criterion of the baby and to remind them to fill out the daily contact logbook and the weekly feeding and sleep logbook. Also, the researcher will ask if they have any questions or comments. If the mother is in the SSC condition, the researcher will encourage her to provide daily SSC to the infant.
Assessment on week two after birth
Thirteen days after birth, all mothers will receive an e-mail or text message to remind them to fill out the additional questionnaires, the 72-h infant crying and sleep logbook, the maternal sleep logbook, and to collect an infant stool sample the next day. Fifteen days after birth, all mothers will be telephoned to ask for questions or comments related to the data-collection on week 2. Also, the home visit on week 5 will be arranged, preferably 4 days after the infant becomes 5 weeks of age.
Week three and week four after birth
Twenty-one days and 28 days after birth an e-mail or text message will be sent to the mother to remind her to fill out the daily contact logbook, the weekly feeding and sleep logbooks, and she will be asked for any questions or comments. The mothers in the SSC condition will be encouraged to provide daily SSC to the infant.
Home visit on week five after birth
On 34 days after birth, the experimenter will remind the mother to fill out the additional questionnaires, the 72-h infant crying and sleep logbook, the maternal sleep logbook, and to collect an infant stool sample on week 5. One day before the expected home visit an e-mail or text message will be sent to the mother to reconfirm the home visit. During the home visit, the mother will bathe her infant as usual. Saliva will be collected from both the mother and infant before and two times (25 and 40 min) after the bathing session. The bathing session will be videotaped to observe the quality of maternal caregiving behavior from tape. Also, the researcher will copy the logbook of the maternity carer from the first week after birth. In addition, a hair sample will be collected from the mother for the assessment of maternal physiological stress levels. The experimenter will collect all study questionnaires, logbooks and samples to take back to the lab.
Assessment on week twelve after birth
Between week 5 and week 12, the mother will be reminded on week 7 and week 9 to fill out the short weekly questionnaire on infant contact, feeding, and sleep by e-mail or text-message. On week 12, the experimenter will send an e-mail to the mothers to remind her to fill out the digital version of the additional questionnaires and to fill out the 72-h infant crying and sleep logbook and the maternal sleep logbook. Afterwards, the mothers will send the logbooks and a copy of the growth curve of the well-baby clinic by post.
Follow-up assessment on one year after birth
One week before the child’s first birthday, all mothers will be telephoned to explain the study procedure on 1 year after birth and the experimenter will send a birthday card and information related to the stool sample to the mother. Also, a digital version of the additional questionnaires will be sent to the mothers by e-mail. Afterwards, the experimenter will visit the home to collect a stool sample and copy the infant’s growth curve from the well-baby clinic logbook. During this short visit, the mother will also receive the debriefing of the study.
All information will be stored with ID code numbers to maintain participant confidentiality. The ID code numbers will be unrelated to participants’ identifiers, except in a central file with the participants’ contact details. All records that contain names or other personal identifiers, such as informed consent forms, will be stored separately from study records identified by the ID code number. All study-related information on paper, including logbooks, questionnaires, and administrative forms, and the maternal hair samples will be securely stored in locked file cabinets in areas with limited access. Biological specimens, including maternal and infant saliva samples and infant stool samples, will be stored in medical refrigerators in the laboratory area, with limited access, of the Behavioural Science Institute. Digital and online information will be secured with password-protected access systems. Two investigators will check the imported data values before the data analyses. Only the principal investigators will be given full access to the data. The Behavioural Science Institute is currently working on an open access database. The entire dataset of this study will be included in this database after publication of all study reports. The dataset will only be shared without participant identifiers.
Data will be handled according to standard procedures. Demographic characteristics and study outcomes will be described for each treatment group using means and standard deviations for continuous outcomes. Proportions for categorical data will be provided. The pattern of missingness will be checked before the analyses. All measures will be controlled for outliers and checked for normality. Skewed continuous outcomes will be transformed. The level of significance (p -value) is set at p < .05 in all analyses.
We will conduct intention-to-treat analyses, in which participants are compared according to the group they were randomly assigned to regardless of participants’ compliance, including SSC protocol adherence, or withdrawal from the study, and analyses on imputed datasets based on the multiple imputation method . Primary and secondary outcomes, that will be examined once, will be compared within multivariate analyses of covariance. Multilevel mixed models will be used for repeated measures. Microbiota composition will be examined with the Pearson’s moving window correlation. Microbiota diversity will be calculated with the Simpson’s reciprocal index of diversity (1/D). The Benjamini and Hochberg method will analyse differences between the SSC group and the control group. The analyses will be adjusted for potential confounding factors identified a priori (see Table 3). Structural equation models will be used to examine the mediation effect of the potential underlying mechanisms, maternal oxytocin concentrations and infant intestinal microbiota, on maternal and infant outcomes, respectively.
Data will be analysed when all the data is collected. The principal investigators will make every attempt to reduce the interval between the completion of data collection and the release of study results to a minimum. The principle investigators will justify names for authorship regarding topics suggested for presentation or publication. Data will only be reported study-wide. The study results will be released in a study-wide manner to participants after publication of the results. Also, the study results will be released to the general public by several channels, including international high impact journals and, at a national level, by oral presentations in health care organizations to inform nurses, midwifes, pediatricians and mental healthcare practitioners about this intervention method.